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3. Results

3.1. Population disposition

A total of 66,726 patients participated in A1chieve®, of which 6323 switched their insulin therapy from BHI 30 ± OGLDs to BIAsp 30 ± OGLDs. There were 991withdrawals (15.7%) from this group (585 individuals lost to contact, 401 for other reasons [including ‘investigator dropout’ in 120 cases and ‘pages not retrievable’ in 163 cases] and five due to ADRs). Therefore, 5332 people completed the study. The efficacy analysis set (EAS), which included all individuals with at least one measurement of FPG, PPG, most recent HbA1c, weight or hypoglycaemic events at baseline and final visit and who maintained the same study insulin during the study, comprised 5200 people. A total of 1123 individuals were excluded from the EAS due to missing endpoint data at baseline and/or final visit (n=991) and/or not maintaining BIAsp 30 treatment throughout the study (n=148).

3.2. Baseline characteristics

Of the 6323 individuals who started on BIAsp 30, 56.9% were male. The mean age was 55.4 years and diabetes duration was 11.1 years. Mean duration on insulin therapy was 3.3 years. Mean body mass index (BMI) was 27.3 kg/m2 and mean body weight was 74.0 kg (Table 1). There were regional differences, particularly in bodyweight and BMI. The subgroup included a proportion of individuals with various diabetic complications including cardiovascular (33.3%), renal (36.9%), eye (35.7%), foot ulcer (6.1%) and neuropathy (49.7%) at baseline.

3.3. Insulin dose and dosing frequency

The mean BHI 30 dose at baseline was 0.56 (0.25) IU/kg. The mean BIAsp 30 dose at baseline was 0.57 (0.25) U/kg, and increased to 0.62 (0.28) U/kg by the end of study (Week 24). The majority of individuals (89.5%) across all regions were on prior twice-daily BHI 30 treatment. At baseline and Week 24, 86.6% and 84.6% of patients received twice-daily BIAsp 30, respectively. A total of 4.5% of patients were administered once-daily BIAsp 30 at both baseline and Week 24; while 8.8% and 10.0% of patients were administered three-times daily BIAsp 30 at baseline and Week 24, respectively.

3.4. Glycaemic control

Switching from BHI 30 to BIAsp 30 was associated with a significant mean reduction [SD] in HbA1c of 1.7% [−18 mmol/mol] (1.6) from a baseline of 9.1% [76 mmol/mol] (1.7) (p<0.001; Figure 1). At baseline, 373 (6.9%) of individuals who had previously used BHI 30 had an HbA1c <7% [53 mmol/mol]. By Week 24 following the switch to BIAsp 30, 1520 (33.6%) of individuals had an HbA1c <7% [<53 mmol/mol] (p<0.0001). FPG was also significantly reduced by 3.0 (3.5) mmol/l from a baseline of 10.2 (3.4) mmol/l (p<0.001; pre-breakfast data shown in Figure 2). PPG following breakfast was significantly reduced in the overall population and in individual countries by Week 24 versus baseline (Table 2). Comparable PPG reductions from baseline to Week 24 were also observed in post-lunch PG (–4.5 [4.2] mmol/l) and post-dinner PG (–3.7 [3.7] mmol/l) in the overall group (p<0.001 for both reductions).

Fig. 1Mean HbA1c reductions in the overall group and by region. *p<0.001.

References in context

Switching from BHI 30 to BIAsp 30 was associated with a significant mean reduction [SD] in HbA1c of 1.7% [−18 mmol/mol] (1.6) from a baseline of 9.1% [76 mmol/mol] (1.7) (p<0.001; Figure 1).Go to context

FPG was also significantly reduced by 3.0 (3.5) mmol/l from a baseline of 10.2 (3.4) mmol/l (p<0.001; pre-breakfast data shown in Figure 2).Go to context

Table 2Post-breakfast plasma glucose reductions in the overall group and by region.

N

All 2961

China 722

South Asia 1009

East Asia 239

North Africa 198

Middle East/Gulf 724

Post-breakfast PG (mmol/l), mean (SD)

Baseline

14.2 (4.3)

12.9 (4.2)

15.1 (3.9)

14.7 (4.8)

14.1 (4.3)

14.3 (4.4)

Week

24 9.9 (2.8)

9.1 (2.0)

10.8 (3.2)

10.3 (3.4)

10.2 (2.8)

9.2 (2.4)

Change from baseline

–4.3 (4.3)

–3.8 (4.3)

–4.4 (4.0)

–4.3 (5.2)

–3.9 (4.9)

–5.0 (4.2)

[P-value]

[<0.001]

[<0.001]

[<0.001]

[<0.001]

[<0.001]

[<0.001]

References in context

PPG following breakfast was significantly reduced in the overall population and in individual countries by Week 24 versus baseline (Table 2).Go to context

PG, plasma glucose; SD, standard deviation

3.5. Hypoglycaemia

The rate of major hypoglycaemic episodes decreased from 0.69 events per patient year at baseline to 0.03 events per patient year by the end of the study. The rate of minor hypoglycaemic episodes decreased from 5.31 to 2.04 events per patient year from baseline to the end of the study. In total, 335 major hypoglycaemic episodes at baseline were reported by 224 individuals (3.5%), 216 diurnal episodes were reported by 170 individuals (2.7%) and 119 nocturnal episodes were reported by 95 individuals (1.5%). At the end of 24 weeks, four individuals (0.08%) reported 12 major hypoglycaemic episodes including seven diurnal episodes reported by three individuals (0.06%) and five nocturnal episodes reported by two individuals (0.04%). A total of 1042 (16.5%) of individuals reported 2584 minor hypoglycaemic episodes at baseline. By Week 24, 424 individuals (8.0%) reported 838 minor hypoglycaemic episodes.

3.6. Serious adverse drug reactions

Five SADRs (hypoglycaemia) were reported by five patients (0.1%); two in the North Africa and three in the Middle East/Gulf regions. Twenty-two individuals (0.3%) reported 24 SAEs. These included seven hypoglycaemic events, four cardiac disorders (two congestive cardiac failures, one cardiogenic shock and one myocardial infarction), three gastrointestinal disorders (one abdominal pain, one diarrhoea and one vomiting), three infections (two lung and one streptococcal septic arthritis), three malignant neoplasms, one chronic renal failure, one respiratory failure, one neuropathic ulcer and one angioplasty. Relationship to study drug was assessed as unlikely for 19 events, possible for one event (hypoglycaemia) and probable for four events (hypoglycaemia). SAEs were assessed as severe (11), moderate (10) or mild (3).

3.7. Bodyweight

Overall, there was an increase in bodyweight of 0.1 (3.3) kg from baseline to Week 24 (China +0.5 kg, South Asia 0 kg, East Asia +0.6 kg, North Africa +0.5 and Middle East/Gulf –0.4 kg).

3.8. Quality of life

An improvement in QoL (SD) was observed from a baseline of 64.0 (16.3) to 76.5 (11.9) at the end of study as measured by a visual analogue scale 0–100 with 0=worst and 100=best imaginable health state.

3.9. Reasons for changing therapy

The most common reason for switching to BIAsp 30 was to improve glycaemic control (91.4%). Other reasons were: to try a new insulin (35.3%), to reduce the risk of hypoglycaemia (34.3%), to reduce PG variability (29.3%) and dissatisfaction with current therapy (26.0%).